Cascade process, reaction mechanism

The mechanism of these MCRs involving Meldrum s acid should include Knoevenagel condensation and Michael addition cascade process [100, 113] (Scheme 37). To form positional isomeric reaction product, arylliden derivatives of Meldrum s acid are attacked by exocyclic NH2-group instead of endocyclic nucleophilic center. 

A unique five-component cascade thiocarbonylation reaction (two molecules of bicyclopropylidene 288, one molecule of bromothiophenol 289, and two molecules of CO) was successfully carried out to give the lactone 290 in 55% yield in one step (Scheme 41). A proposed mechanism for this cascade process is illustrated in Scheme 41. 

Abstract Ruthenium holds a prominent position among the efficient transition metals involved in catalytic processes. Molecular ruthenium catalysts are able to perform unique transformations based on a variety of reaction mechanisms. They arise from easy to make complexes with versatile catalytic properties, and are ideal precursors for the performance of successive chemical transformations and catalytic reactions. This review provides examples of catalytic cascade reactions and sequential transformations initiated by ruthenium precursors present from the outset of the reaction and involving a common mechanism, such as in alkene metathesis, or in which the compound formed during the first step is used as a substrate for the second ruthenium-catalyzed reaction. Multimetallic sequential catalytic transformations promoted by ruthenium complexes first, and then by another metal precursor will also be illustrated. 

Terpene synthases, also known as terpene cyclases because most of their products are cyclic, utilize a carbocationic reaction mechanism very similar to that employed by the prenyltransferases. Numerous experiments with inhibitors, substrate analogues and chemical model systems (Croteau, 1987 Cane, 1990, 1998) have revealed that the reaction usually begins with the divalent metal ion-assisted cleavage of the diphosphate moiety (Fig. 5.6). The resulting allylic carbocation may then cyclize by addition of the resonance-stabilized cationic centre to one of the other carbon-carbon double bonds in the substrate. The cyclization is followed by a series of rearrangements that may include hydride shifts, alkyl shifts, deprotonation, reprotonation and additional cyclizations, all mediated through enzyme-bound carbocationic intermed iates. The reaction cascade terminates by deprotonation of the cation to an olefin or capture by a nucleophile, such as water. Since the native substrates of terpene synthases are all configured with trans (E) double bonds, they are unable to cyclize directly to many of the carbon skeletons found in nature. In such cases, the cyclization process is preceded by isomerization of the initial carbocation to an intermediate capable of cyclization. 

The addition of thiyl and sulfonyl radicals, either in stoichiometric or in catalytic amounts, is used as the first step of tandem processes which have been widely applied to prepare carbocyclic compounds. The catalytic procedure will be further described in Section 5.5.4.3 during the discussion of cascade processes involving fragmentation reactions. The mechanism of the stoichiometric procedure, which can involve thiols, disulfides, or any sulfonyl radical precursor, is represented in Scheme 7. It consists of (i) the initial addition step, (ii) the cyclization with formation of the final radical species, and (iii) the quenching of the final radical to give the product. 

Several very interesting cascade processes have also been developed under phase-transfer catalysis which are initiated by a conjugate addition reaction, although the number of reports is remarkably more limited compared to other organocatalytic cascades proceeding via other different mechanisms of activation. Representative examples will be presented in the following pages. 

The ability of A -heterocyclic carbenes to activate a,p-unsaturated carbonyl compounds via the formation of the corresponding Breslow intermediate, which plays the role of a homoenolate nucleophile, has also been applied to a cascade process involving a formal intramolecular Michael reaction/oxidation/ lactonization, leading to the formation of complex tricyclic carbon frameworks starting from a bifunctional substrate containing an enone and an a,p-unsa-turated aldehyde side chain linked to each other via a benzene tether (Scheme 7.82). The reaction involved a complex multistep mechanism which started with the activation of the enal by the catalyst, forming the Breslow intermediate, which subsequently underwent intramolecular Michael reaction and next the generated enol-type intermediate reacted intramolecularly with the... 

Catalytic reactions constitute a special type of reaction mechanism in which a chemical amplification takes place. With very low catalyst concentrations a significant amount of reaction product can be measured, enhancing the analytical sensitivity of the measurements. In general, these reactions are not amplification reactions. However, in some enzymatic reactions, a series of enzymes and other co-factors act on each other in a sequential fashion, providing a cascade reaction or, in a cyclic process, providing a rapid, amplified response of the small initial signal, and these processes can be considered examples of amplification reactions. 

In this section, only examples of Mizoroki-Heck reactions where a proper addition of the cr -aryl- or a -alkeny Ipalladium(II) complex to a double bond of an alkene or alkyne occurs are considered. As a consequence, an often-met deviation from the classic Mizoroki-Heck mechanism, the so-called cyclopalladation, will not be treated in further detail [12, 18]. However, as it is of some importance, especially in heterocycle formation and mainly because it will be encountered later during polycyclization cases, it shall be mentioned briefly below. Palladacycles are assumed to be intermediates in intramolecular Mizoroki-Heck reactions when j3-elimination of the formed intermediate cannot occur. These are frequently postulated as intermediates during intramolecular aryl-aryl Mizoroki-Heck reactions under dehydrohalogenation (Scheme 6.1). The reactivity of these palladacycles is strongly correlated to their size. Six-membered and larger palladacycles quickly undergo reductive elimination, whereas the five-membered species can, for example, lead to Mizoroki-Heck-type domino or cascade processes [18,19]. 

From this scheme, electropolymerization proceeds through successive electrochemical and chemical steps. In the terminology of electrochemical reaction mechanisms, this chain-propagation process corresponds to a cascade of ECE steps. The chain growth is terminated either when the radical cation of the growing chain becomes too unreactive or, more likely, when the reactive end of the chain becomes sterically blocked from further reaction [61]. 

Fig. 6.4 Modified Jablonski diagram for an organic molecule showing ground and excited states and intramolecular photophysical processes from excited states. Radiative ntK esses—fluorescence (hvf) and phosphorescence (hvp) are shown in straight lines, radiationless processes— internal conversion (1C), inter system crossing (ISC), and vibrational cascade (vc) are shown in wavy lines. Adapted with permission fiom (Smith MB, March J 2006 March s Advanced Organic Chemistry Reactions, Mechanisms and Stiucmres, 6th Ed., John Wiley, New York). Copyright (2007) John Wiley Sons...

Cinnamils (162) have surprisingly been found to evolve towards 2,3,8-triaryl vinyl fulvenes (163) and o-terphenyl derivatives (164) under NHC catalysis. The formation of these products has been rationalized via a mechanism involving a complex cascade process. Finally, a mechanistic investigation has been carried out on the NHC-catalysed aerobic oxidative esterification of aromatic aldehydes.Aryloin species have not only been identified as key intermediates of such oxidative reactions, but most importantly is that they have been shown to be the species which react with oxygen in the air and not the Breslow intermediates as previously suggested. 

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